Substituted Chalcone Derivatives Research Articles

Femtosecond nonlinear optical investigations of nitro chalcones-doped PMMA thin films for optical limiting and photonic applications

Herein we present the linear and third-order nonlinear optical properties of two nitro substituted chalcone derivatives [3-(4-fluorophenyl)− 1-(3-nitrophenyl) prop-2-en-1-one and (2E,4E)− 1-(3-nitrophenyl)− 5-phenylpenta-2,4-dien-1-one; abbreviated as F3NC and Ci3NC, respectively] doped PMMA polymer thin films. The chemical spray pyrolysis method was adopted to prepare the films at three different doping concentrations (5 wt%, 10 wt%, 15 wt%). The linear optical studies were performed using UV-Visible-NIR spectra, and surface roughness using AFM technique. Hirshfeld surface analysis was adopted to understand the intermolecular interactions. The third-order nonlinear optical properties were investigated using Z-scan method under Ti:Sapphire femtosecond (fs) laser pulses (∼150 fs, 80 MHz, 800 nm). Open and closed aperture Z-scan curves indicated the presence of two-photon assisted reverse saturable absorption and self-defocusing effect, respectively. The calculated nonlinear refraction (n2), nonlinear absorption (β) coefficients and third-order susceptibility [χ(3)] were found to be in the order ∼10−12 cm2 W−1, ∼10−8 cm W−1 and ∼10−11 e.s.u., respectively. We observed increase in nonlinearity of the films with increased chalcone doping concentration. Among the doped chalcones, F3NC doped films exhibit a higher nonlinearity than Ci3NC doped films. The observed results reveal that chalcone-doped PMMA thin films are possible materials for optical limiting and photonic applications.

Synthesis and Biological Evaluation of Nitro-substituted chalcones as potent Antibacterial and Antifungal agents

In recent years, complications of micro-organisms, which becomes drug-resistant, have extended dreadful level across the globe. One of the significant challenges in drug discovery to overcome the increased development of drug resistance is developing novel chemical moieties that advantageously comprise chemical features different from existing chemical entities. This communication presents the synthesis, docking, and antibacterial and antifungal evaluation of nitro chalcones. New series of nitro substituted chalcone derivatives (1-12) were synthesized via Claisen-Schmidt condensation using substituted acetophenone and various substituted benzaldehydes in the presence of base and ethanol. Spectral analysis of the synthesized compounds was carried out using 1H-NMR, IR, 13C-NMR and HRMS methods. Synthesized derivatives were evaluated for antimicrobial potency via the microdilution method against two Gram-positive and two Gram-negative bacterial strains and two fungal strains. All compounds showed promising antimicrobial potency. However, compound 6 was the most potent derivative of the series against all the tested antibacterial strains. Compounds 10 and 12 were found to be the most potent analogues of the series against all the tested antifungal strains. All the synthesized derivatives had good antifungal potency in comparison to the antibacterial potency. Based on the preliminary study results, the study concluded that the synthesized chalcones derivatives promise antimicrobial activity that may be further investigated to achieve antimicrobial lead.

DFT Study of Regio- and Stereoselective 13DC Reaction between Diazopropane and Substituted Chalcone Derivatives: Molecular Docking of Novel Pyrazole Derivatives as Anti-Alzheimer's Agents.

In the present work, a combination of experimental and density functional theory (DFT) investigation of the (3+2) cycloaddition reactions of diazopropane with chalcone derivatives was reported. All calculations were performed using several DFT approaches (B3LYP, M06, M06-2X) and 6-311+G(d, p) basis set. Based on the NMR, MS analyses and IRC calculations, the pyrazole derivatives are the kinetic adducts over the oxadiazoles. The use of two equivalents of diazopropane leads to thermodynamical products. A molecular docking analysis was performed to investigate the efficiency of the obtained products against selected drug targets in anti-Alzheimer ligand-receptor interactions. We revealed that the ligands selected were bound mainly to the catalytic (CAS) and peripheral (PAS) anionic sites of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors, respectively. The selected ligands 1, 3, 4 and P14 may act as the best inhibitors against Alzheimer's disease (AD).

SYNTHESIS, CHARACTERIZATION AND ANTI-TUBERCULAR ACTIVITY OF 1, 3- THIAZINE DERIVATIVES

Due to their potent biological activity, heterocyclic compounds have been used extensively in pharmacological research.Researchers' interest has been drawn to the heterocyclic molecule thiazine, which has four carbon atoms, one nitrogenatom, and one sulphur atom. It has interesting pharmacological properties. In the present work, a series of new thiazinederivatives were synthesized from substituted chalcone derivatives. Starting material was acetophenone derivatives. Thestructures of these compounds were confirmed by IR, NMR, Mass and elemental analysis. The synthesized compounds(IVa-IVe) were screened for anti-tuberculosis activity against Mycobacterium tuberculosis and the results show that some ofthese derivatives possess good activity against Mycobacterium tuberculosis.

Discovery of chalcone derivatives as potential α-glucosidase and cholinesterase inhibitors: Effect of hyperglycemia in paving a path to dementia

In the present study, a series of fascinating chalcone derivatives 1C-14C has been designed and synthesized by Claisen-Schmidt condensation. The target compounds were screened for in vitro α-glucosidase and cholinesterase inhibitory activities. For the first time, the enzyme inhibitory activities of the target derivatives were assessed for antihyperglycemic and neuroprotective activities on streptozotocin (STZ) induced diabetic animal models using in vivo mechanism-based assays. Based on α-glucosidase and cholinesterase inhibitory activities, the compounds 2C, 3C, 13C and 14C were chosen in vivo for further evaluation of antidiabetic and neuroprotective activities in STZ-induced diabetic Wistar rats. All these evaluated compounds demonstrated significant antidiabetic and antiamnesic activities and found nontoxic in nature. The target compounds were then tested in vivo for cognitive function in a STZ-induced amnesic animal paradigm, where four compounds 2C, 3C, 13C, and 14C considerably reduced the amnesic effects as measured by the Y-Maze Paradigm and novel object discrimination (NOD) tasks. Furthermore, the structure-activity relationship of these substituted chalcone derivatives was established. According to kinetic studies, 2C and 7C have Ki values of 0.017±0.00078 µM and 0.00060±0.00004 µM, respectively, and were competitive inhibitors of cholinesterase and α-glucosidase. Molecular docking study revealed that the co-crystallized ligand and potent compounds exhibited same binding orientation within the target enzyme's active site (α-glucosidase (PDB ID: 3AJ7), AChE (PDB ID: 1ACL) and BChE (PDB ID: 4TPK)). The QSAR studies were conducted based on anti-glucosidase and anti-cholinesterases (AChE, BChE) assays. The value of coefficient of multiple determinant (R2) 0.9999 depicts a strong relationship between 1C-14C structures and selected properties. Most of these substances are selective inhibitors of cholinesterase that may be used for age-related problems and to treat the progressive neurodegenerative disorder.

Synthesis, Cytotoxicity and Molecular Docking Studies of Chalcone Incorporated 1,2,3-Triazol-1,3,5-Triazin-Quinazoline as Anti-Cancer Agents

Chalcone derived 1,2,3-Triazol-1,3,5-Triazin-Quinazoline acts as an anti-cancer agent. It has widespread applications in the medicinal field. We have designed and prepared a novel series of different substituted chalcone derivatives of 1,2,3-triazol-1,3,5-triazin-quinazoline (13a-j). Their chemical structures of chalcone derivatives were further confirmed by spectroscopic techniques (Mass, 1H and 13C NMR). Further, these compounds (13a-j) were screened for their cytotoxic profiles against four different human cancerous cell lines such as PC3 (prostate cancer), A549 (lung cancer), MCF-7 (breast cancer), and DU-145 (prostate cancer) using MTT assay, etoposide acts as a positive control and the cytotoxicity profiles were expressed in IC50 µM values. All the synthesized compounds exhibited good to moderate cytotoxicity activities. Out of all the compounds, specifically 13a compound exhibits good cytotoxicity values in four different cell lines with IC50 values of 0.0071 µM, 0.0094 µM, 0.0083 µM and 0.086 µM respectively. We conclude that 13a displayed good anti-cancerous activity among all the compounds (13b-j). In order to predict the binding interactions between the active site of the tubulin complexed with colchicine as a reference ligand, molecular docking was performed between the compound 13a, into the crystal structure of the tubulin complex with PDB ID: 1SA0 using Maestro 8.5 (Schrodingers LLC, installed in RHEL 5.0 platform. Maestro 10.1). The molecule 13a showed strong interactions due to H bonding, pi- pi interaction and hydrophobic interactions with active site amino acids. With these results, we conclusively validated the selected structural analogues can act as potential anti-cancerous agents.

SYNTHESIS, In-vitro AND In-silico ANTICANCER ACTIVITY STUDIES OF METHOXY SUBSTITUTED TETRALONE-BASED CHALCONE DERIVATIVES

Chalcones are organic compounds with numerous biotic activities such as anticancer, antibacterial, and antifungal. Using the Claisen-Schmidt condensation reaction, three methoxy substituted chalcone derivatives were synthesized and crystallized using the slow evaporation method. Cytotoxicity evaluation showed that all three compounds were almost inoffensive to VERO cell lines and exhibited excellent anticancer activity on breast cancer (MCF-7) cell lines. Molecular docking analysis confirmed that all three molecules fit well at the active site of the target protein with PDB ID: 1M17. In silico pharmacokinetic analysis reveals that the compounds satisfied Lipinski’s rule of five and can be recommended as oral drug candidates. ADMET properties of the organic synthesized compounds revealed the efficacy of the compounds to be considered as drug candidates for treating breast cancer after in-vivo experiments and clinical authentication.

Design, Synthesis and Application of Tetraphenylethene Substituted Chalcone Derivatives as Ph Indicator

Design, Synthesis and Application of Tetraphenylethene Substituted Chalcone Derivatives as Ph Indicator

Drug-Receptor Interactions of New Isoxazole Scaffold against Breast and Skin Cancer Cell Lines

The electron rich oxygen and nitrogen exists at 1, 2 positions in a five membered ring system is known as isoxazole, an active pharmacophore. They are reported to be interesting synthons to synthesize various useful scaffolds of interesting biological activities. Herein, we report the synthesis of isoxazoles from ethoxy substituted chalcone derivatives on reaction with hydroxylamine hydrochloride in basic medium. All the compounds are characterized by spectroscopic methods. The present study is an effort to extend the utility of virtual drug-receptor interaction of isoxazoles on the active site of target inhibitor bound cytochrome P450 family oxidoreductase [PDB: 3PM0] for breast cancer cell line and pirin inhibiting target [PDB: 3ACL] for skin cancer cell lines respectively. Both the chloro and bromo substituted derivatives showed maximum interactions with minimum docking scores. In silico ADME–toxicity evaluation to predict the preliminary pharmacokinetic and toxicity profile of the synthesized compounds is also conducted. Copyright © VBRI Press.

Computational and Spectral Discussion of Some Substituted Chalcone Derivatives

The substituted chalcone derivatives 1–7 have been synthesized, and spectroscopic characterization were done as done using the experimental FT-IR, UV-Vis, GC-MS, 1D NMR spectroscopy. The favored conformation of substituted chalcone 3 was predicted theoretically by geometry optimization structure selected geometrical parameters and molecular properties such as NBO, AIM, HOMO-LUMO, MEP surface, and atomic charges were derived from optimized structures. The 1H and 13C NMR spectral data had been additionally computed using the Gaussian-09 package and compared with the experimental values. The antibacterial and antifungal activity was derived by the disc diffusion method.

Synthesis, Molecular Docking and Biological Activity Evaluation of Alkoxy Substituted Chalcone Derivatives: Potential Apoptosis Inducing Agent on MCF-7 Cells.

In this contribution, a series of alkoxy substituted chalcones were successfully designed, synthesized, spectroscopically characterized and evaluated for their cytotoxicity potential in inhibiting the growth of MCF-7 cells. In order to investigate the influence between electron density in conjugated π-systems and biological activities, different withdrawing substituents, namely Nitro (NO2), Cyano (C≡N) and trifluoromethyl (CF3) were introduced in the chalcone-based molecular system. All the derivatives were then tested on MCF-7 cell line using the fluorescence microscopy-based cytotoxicity analyses. The preliminary findings showed that both -NO2 and -CF3 substituents revealed their potential to inhibit the growth of MCF-7 with IC;50 values of 14.75 and 13.75 μg/ml, respectively. In addition, the morphological changes of MCF-7 cells were observed in response to alkoxy substituted chalcone treatment through an induction of apoptosis pathway with cell blebbing, phosphatidylserine exposure and autophagic activity with acidification of lysosomal structure. Intermolecular interaction based on in silico investigation on nitro, trifluoromethyl and cyano based chalcones exhibited several types of interactions with tumor necrosis factor receptor (PDB: 1EXT) protein and high hydrogen bond in the molecule-receptor interaction have given significant impact towards their toxicity on MCF-7 cells. Significantly, these types of chalcones exhibited ideal and high potential to be further developed as anti-cancer agents.

“SYNTHESIS AND MESOMORPHIC PROPERTIES OF NEWLY IMIDAZOLIUM IONIC LCS BASED ON CHALCONE LINKING GROUP”

A newly imidazolium linked chalcone ionic LCs (5a-5f) based on two phenyl rings have been synthesized by the quaternization of 1-methylimidaazole and 3,4,-dialkoxy substituted chalcone derivatives. The mesomorphic properties of these compounds were observed by optical polarized light microscopy (POM) and confirmed by differential scanning calorimetry (DSC) analysis. All synthesized compounds exhibited mesogenic properties on heating and cooling condition. Thermal stability of smectic and nematic phase of present ILCs are higher as compared to series-1. Their chemical structures were identified by using 1H NMR and IR spectroscopy.

Synthesis, antibacterial and computational studies of Halo Chalcone hybrids from 1-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one

In an endeavor to develop antibacterial agents, a series of six 1,4-benzodioxan-6-yl substituted chalcone derivatives were synthesized by the base-catalyzed Claisen-Schmidt reaction of the 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one with fluoro and chloro substituted aromatic aldehydes. The synthesized products were characterized by FT-IR, 1H NMR, and 13C NMR spectroscopic techniques. The density functional theory (DFT) calculations were performed using the B3LYP functional with the 6-31G(d,p) basis set for the optimization of molecular geometries and frequency calculations. The CAM-B3LYP functional with a 6-31G(d,p) basis set was used in time-dependent density functional theory (TD-DFT) calculations for the electronic absorption studies. Optimized geometries, frontier molecular orbitals, and global reactivity descriptors' specifications were computed and addressed. The simulated electronic absorption spectra were recorded in the gas phase and dichloromethane (DCM) solvent. The electronic configurations, oscillator strengths, and excited state energies were also discussed. The theoretical UV–Vis and IR vibrational analyses were equated with the experimental findings for the assignment of absorption bands. The synthesized chalcones were evaluated for in vitro antibacterial activities against two Gram positive bacteria (Bacillus subtilis and Staphylococcus aureus) and two Gram negative bacteria (Escherichiacoli and Proteus vulgaris). The DFT simulations were correlated with the antibacterial findings and it was discovered that they were highly helpful in the designing antibacterial agents and to establish the structure–activity relationship. Theoretical calculations are in good correlation with the in vitro antibacterial results.

Study of CuSCN Catalyzed Conjugate Addition Reactions of Grignard Reagents to Substituted Chalcones with Dilithium Tetrachloromanganate and their Biological Activities

The regioselective 1,4-addition reactions of copper thiocyanate catalyzed Grignard reagents to the substituted chalcones are reported. The homogeneous solution of dilithium tetrachloromanganate is used to transmetallate magnesium by using manganese. It adds regio-selectively to substituted chalcone derivatives and forms 1,4-addition products with higher yield under nitrogen atmosphere and at a lower temperature. It have been observed that manganese from dilithium tetrachloromanganate reagent replaces magnesium from Grignard reagent and adds regioselectively by 1,4-addition manner utilizing copper thiocyanate as a catalyst. The course of the reaction in the absence of dilithium tetrachloromanganate reagent was also studied and obtained a mixture of 1,2-addition and 1,4-addition products. In presence of dilithium tetrachloromanganate reagent, a good regio-selectivity and higher yield of desired 1,4-addition product were obtained. All the synthesized compounds were also evaluated for their antibacterial activity against Staphylococcus aureus (Gram-positive), Escherichia coli (Gramnegative) and antifungal activity against Aspergillus niger.

Design, Synthesis, and Antibacterial and Antifungal Activities of Novel Trifluoromethyl and Trifluoromethoxy Substituted Chalcone Derivatives.

Despite the availability of many drugs to treat infectious diseases, the problems like narrow antimicrobial spectrum, drug resistance, hypersensitivities and systemic toxicities are hampering their clinical utility. Based on the above facts, in the present study, we designed, synthesized and evaluated the antibacterial and antifungal activity of novel fluorinated compounds comprising of chalcones bearing trifluoromethyl (A1–A10) and trifluoromethoxy (B1–B10) substituents. The compounds were characterized by spectroscopic techniques and evaluated for their antimicrobial activity against four pathogenic Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Escherichia coli and Bacillus subtilis) bacterial and fungal (Candida albicans and Aspergillus niger) strains. In this study, the compounds with trifluoromethoxy group were more effective than those with trifluoromethyl group. Among the 20 fluorinated chalcones, compound A3/B3 bearing an indole ring attached to the olefinic carbon have been proved to possess the most antimicrobial activity compared to the standard drugs without showing cytotoxicity on human normal liver cell line (L02). Further, the minimum inhibitory concentration (MIC) for A3/B3 was determined by serial tube dilution method and showed potential activity. These results would provide promising access to future study about the development of novel agents against bacterial and fungal infections.

Iodine-Catalyzed Addition of Thiophenol to Isoindolsubstitue Chalcones

Kalkon ve isoindol türevleri önemli biyolojik aktivitelere sahip bileşiklerdir. Bu iki birimi aynı yapıda taşıyan hibrit moleküllerinde biyolojik aktivite gösterdikleri bilinmektedir. Ayrıca β-merkaptanlar bazı biyoaktif bileşiklerin sentezi için başlangıç materyali olarak kullanılmaktadırlar. Bu çalışmada, isoindolsübstitüe-kalkon türevlerine (3a-j) moleküler iyot katalizörlüğünde tiyofenol katılarak yeni β-merkapto karbonil bileşikleri, ((3aR,4S,7R,7aS)-2-(4-(3-(feniltiyo)-3-(aril)propanol)fenil)-3a,4,7,7a-tetrahidro-1H-4,7-metanisoindol-1,3(2H)-dion) (5a-j) yüksek verimler ile elde edildi. Elde edilen yeni bileşiklerin yapıları 1H-NMR, 13C-NMR, FT-IR ve Elementel Analiz spektroskopik yöntemleri kullanılarak aydınlatıldı.

A long-chain based bromo and methyl substituted chalcone derivatives; experimental and theoretical approach on nonlinear optical single crystals

In the present work, growth of single crystals of chalcone derivatives {4-[(1E)-3-(4-methylphenyl)-3-oxoprop-1-en-1-yl]phenyl 4-methylbenzene-1-sulfonate} (4M1PMS) and {4-[(1E)-3-(4-bromophenyl)-3-oxoprop-1-en-1-yl]phenyl4-methylbenzene-1-sulfonate} (4BPMS), at room temperature is reported. The spectroscopic techniques are used to identify the presence of functional groups in the materials. The single-crystal XRD and powder XRD analysis reveals that 4M1PMS belongs to non-centrosymmetric () and 4BPMS belongs to centrosymmetric crystalline system. The molecular structures exhibit C–H…O and π...π intermolecular interactions. From UV/VIS/NIR spectroscopic studies, it is found that both samples have bathochromic shifts in linear absorbance (cut-off region) spectra. The broad emission region involved in several sharp emission peaks in blue region, exhibits a blue light emission property, as observed from photoluminescence study, in both the samples. The thermal stability of the materials were studied by TGA/DTA techniques and crystals were thermally stable until the melting point. In NLO study, 4M1PMS crystal has shown SHG efficiency 2.2 times that of KDP crystal. In addition, electronic contribution in hyperpolarizability (first order and second order) tensors of both the compounds were computed theoretically by M06-2X functional at DFT level. The open/closed aperture Z-scan technique were performed to evaluate third order nonlinear optical materials by measuring experimental parameters such as nonlinear absorption/refraction and calculate second-order hyperpolarizability with corresponding third-order nonlinear optical susceptibility of 4M1PMS and 4BPMS. The surface damage threshold studies of 4M1PMS and 4BPMS were performed by Q-switched Nd:YAG laser at 532 nm.

Synthesis and characterization of some novel fluoro and methoxy substituted chalcone derivatives via nucleophilic aromatic substitution

Synthesis and characterization of some novel fluoro and methoxy substituted chalcone derivatives via nucleophilic aromatic substitution

Synthesis, characterization and significant optoelectronic parameters of 1-(7-methoxy-1-benzofuran-2-yl) substituted chalcone derivatives

A new series of benzofuran substituted chalcone derivatives was synthesized by the base-catalyzed Claisen-Schmidt reaction of the 1-(7-methoxy-1-benzofuran-2-yl) ethanone with different aromatic aldehydes to yield 1-(7-methoxy-1-benzofuran-2-yl) substituted chalcone derivatives 3a-e. We investigated in detail the UV spectra, mass extinction, band structure, refractive indices, optical fracture and conductance properties of the benzofuran substituted chalcone derivatives 3a-e. The benzofuran substituted chalcone derivatives 3a-e compounds are suitable for electronic and optoelectronic devices. According to obtained results the electron-withdrawing groups are attached to the ring A, 3c compound gives the worst results for related devices, while the electron-donating groups are attached to the ring A, 3b compound gives the best results for related devices.

Single crystal X-ray studies and Hirshfeld surface analysis of ethoxy phenyl substituted chalcone derivatives

Abstract The single crystal X-ray of three chalcone derivatives, (2E)-3-(2-chlorophenyl) -1-(4-ethoxyphenyl) prop-2-en-1-one (I), (2E)-3-(3-chlorophenyl)-1-(4-ethoxyphenyl)prop-2-en-1-one (II) and (2E)-1-(4-ethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (III) was determined. The compound (I) crystallized in triclinic P−1 crystal system and in the asymmetric unit of the compound (I), two molecules were present. The conformational differences between molecule A and B indicated with the dihedral angles of 3.47 (2)° (A) and 8.12 (16)° (B), measured between chlorophenyl ring (C1A/B-C6A/B) and methoxy phenyl (C10A/B–C16A/B). Similarly the compound (II) crystallized in monoclinic P−1 crystal system and in the asymmetric unit of the compound (II), two molecules were present. The conformational differences between molecule A and B with the dihedral angles of 4.50 (11)° (A) and 3.94 (11)° (B) was measured between terminal phenyl rings. The compound (III) crystallized in monoclinic, P21/n, with a dihedral angle between two terminal phenyl rings is 13.18 (7)°, indicating the near planarity of the compound. The intramolecular hydrogen bond of the types C—H…O is observed in all compounds (I), (II) and (III). In the crystal structures (I), (II) and (III), C—H…π intermolecular interaction was found in all compounds. The intermolecular hydrogen bond of the type C—H…O was present in compounds (I) and (II). The Hirshfeld surface analysis was carried for compounds (I), (II) and (III). Intercontacts C C, C H, C O, H H and O H were common in all compounds which contributed more to the Hirshfeld surfaces. The electrostatic potential surfaces were drawn to understand electrophilic and nucleophilic regions on the molecule.